Pathogenic Microbiology Commons^™

Investigating Microbial And Host Factors That Modulate Severity Of Clostridioides Difficile Associated Disease, Armando Lerma

Department of Food Science and Technology: Dissertations, Theses, and Student Research

Clostridioides difficile is recognized as one of the most important pathogens in hospital and community healthcare settings. The clinical outcome of infection of toxigenic C. difficile infection (CDI) ranges from asymptomatic colonization to fulminant pseudomembranous colitis and death. In recent studies, it has been suggested that a high proportion of nosocomial CDI cases are transmitted from asymptomatic carriers which might be acting as infection reservoirs. Understanding what causes the different responses to infection could lead to the development of novel prevention and treatment strategies. Although several explanations have been proposed to explain variations in susceptibility, understanding of the exact mechanisms …

The Investigation Of Surface Structures On Various Pathogens And Their Interactions With The Human Immune System, Carmen M. Villalobos

Biomedical Engineering ETDs

The cell surface is the first interface the host immune system encounters and

its investigation has led to a better understanding of cellular biology and types of

pathways that pathogens target in a host cell. The cell surface has evolved to include

many functions such as manipulation of the cytoskeleton, cell signaling, membrane

trafficking, adhesion, and integration into host tissue. The pathogens of interest are

the pathogenic fungus, Candida albicans, and the parasite, Giardia lamblia and we

investigate the consequences of drug treatments on the cell surface, leading to

promising new targets.

Development, Expansion And Role Of Myeloid-Derived Suppressor Cells In Post-Sepsis Immune Suppression, Tuqa Alkhateeb

Electronic Theses and Dissertations

Myeloid-derived suppressor cells (MDSCs) numbers increase significantly in sepsis and are associated with high mortality rates. These myeloid cell precursors promote immunosuppression, especially in the late (post sepsis) stage. However, the mechanisms that underlie MDSC expansion and programming are not completely understood. To investigate these mechanisms, we used a cecal-ligation and puncture (CLP) mouse model of polymicrobial sepsis that progresses from an early/acute proinflammatory phase to a late/chronic immunosuppressive phase. Previous studies in our laboratory showed that microRNA (miR)-21 and miR-181b elevate levels of the transcription factor nuclear factor 1 (NFI-A) that promotes MDSC expansion. We report here that miR-21 …

Utility Of Molecular Tools For The Identification And Characterization Of Infectious Agents, Shih Keng Loong

Student Works (2020-2029)

Molecular tools involving nucleic acid sequence-based detection offer rapid, sensitive and specific identification of bacterial infections, all together instrumental in timely patient management and infection control. Analyses of DNA sequences played a pivotal role in the discovery of novel or uncommon bacterial pathogens. This method can be applied to detect and identify rare and potentially pathogenic bacterial infectious diseases emerging from the interactions between human, animal and the environment. In this study, the 16S rDNA sequencing demonstrated superior utility against the conventional phenotypic identification systems for the identification of rare pathogenic bacteria. Its inability to differentiate between certain bacterial species …

Development Of In Vitro Models To Study The Rapid Extraintestinal Dissemination Of Salmonella., Adarsh Gopinath

Electronic Theses and Dissertations

Salmonella appears in the bloodstream of mice in as little as 15 minutes after oral inoculation and establishes persistent colonies in the spleen and liver. While its pathway to blood is undetermined, this phenomenon is dependent on the activity of Salmonella pathogenicity island 2 (SPI-2) coded type III secretion system (T3SS) and CD18+ phagocytes. We hypothesize that dendritic cells associated with the basal face of the gut epithelium, that are naturally migratory and known to sample for luminal antigens directly transport Salmonella to the bloodstream. This process comprises of at least two phases, dissociation and reverse transmigration. We define dissociation …

Histidine-Triad Hydrolases Provide Resistance To Peptide-Nucleotide Antibiotics., Eldar Yagmurov, Darya Tsibulskaya, Alexey Livenskyi, Marina Serebryakova, Yury I Wolf, Sergei Borukhov, Konstantin Severinov, Svetlana Dubiley

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The Escherichia coli microcin C (McC) and related compounds are potent Trojan horse peptide-nucleotide antibiotics. The peptide part facilitates transport into sensitive cells. Inside the cell, the peptide part is degraded by nonspecific peptidases releasing an aspartamide-adenylate containing a phosphoramide bond. This nonhydrolyzable compound inhibits aspartyl-tRNA synthetase. In addition to the efficient export of McC outside the producing cells, special mechanisms have evolved to avoid self-toxicity caused by the degradation of the peptide part inside the producers. Here, we report that histidine-triad (HIT) hydrolases encoded in biosynthetic clusters of some McC homologs or by standalone genes confer resistance to McC-like …

Virulence Of Drosophila C Virus Increased After A Host Shift And Serial Passage In Drosophila Hosts, Katie A. Johnson

EWU Masters Thesis Collection

The outcomes of novel host-pathogen interactions are unpredictable but can result in epidemics or pandemics. Exploring the initial encounter between a pathogen and a novel host species can elucidate why some pathogens successfully infect and adapt on a novel host when others fail. Much of our understanding of host virulence after host shifts was developed using serial passage experiments (SPEs) in bacteria. Three accepted SPE generalities have emerged: virulence increases on the novel host, the evolved pathogen will become less able to infect its native host, and the pathogen experiences convergent evolution. This study tests the first two generalities using …

The Histoplasma Capsulatum Ddr48 Gene Is Required For Survival Within Macrophages And Resistance To Oxidative Stress And Antifungal Drugs, Logan Blancett

Dissertations

Histoplasma capsulatum(Hc)is a systemic, dimorphic fungal pathogen that affects upwards of 500,000 individuals in the United States annually. Hc grows as a multicellular mold at environmental temperatures; whereas, upon inhalation into a human or other mammalian host, it transforms into a unicellular, pathogenic yeast. The research presented in this dissertation is focused on characterizing the DNA damage-responsive gene HcDDR48. HcDDR48was originally isolated via a subtractive DNA library enriched for transcripts enriched in the mold-phase of Hcgrowth. Upon further analysis we found that HcDDR48is not just expressed in the mold morphotype, but both growth programs …

Elucidating Immune Signaling Of Influenza A Virus And Aspergillus Fumigatus Co-Infections Through Pioneered Model Development, Meagan Danyelle Rippee-Brooks

Graduate Theses/Dissertations

Bacterial co-infections with influenza A virus (IAV) are extremely serious and life-threatening. However, there exists limited understanding about the importance of fungal infections with IAV. Clinical case reports indicate that fungal co-infections do occur and suggest the IAV pandemic of 2009 had a propensity to predispose patients to secondary fungal infections more than previous IAV strains. IAV-fungal co-infections are marked by high mortality rates of 47 to 61% in previously healthy individuals between the ages of 20 and 60. Yet, the variables involved in this co-infection remain undetermined. I achieved effective recapitulation of this co-infection using a C57Bl/6 murine (mouse) …

A High Throughput Assay For The Detection Of Stimulator Of Interferon Genes (Sting) Agonists, Michael J. Ingling

Graduate School of Biomedical Sciences Theses and Dissertations

The innate immune system includes a menagerie of different cell types, each with a different role in the process of monitoring the body for invaders and presenting gathered debris (antigen) to the adaptive immune system. Somatic cells have intracellular receptors for the same purpose. Cancer cells, however, have avoided these methods of detection despite, in many cases, the tumor’s immunogenic traits. Immuno-oncology is a field dedicated to the immunological traits of tumors, more recently finding ways of instigating an immune response against tumors. In this regard, STING, a receptor of cyclic dinucleotides (CDN), has come to the forefront of immuno-oncology. …

A Rapid Viability And Drug‑Susceptibility Assay Utilizing Mycobacteriophage As An Indicator Of Drug Susceptibilities Of Anti‑Tb Drugs Against Mycobacterium Smegmatis Mc2 155, Gillian Catherine Crowley, Jim O'Mahony, Aidan Coffey, Riona G. Sayers, Paul D. Cotter

Department of Biological Sciences Publications

Background: A rapid in-house TM4 mycobacteriophage-based assay, to identify multidrug resistance against various anti-tuberculosis drugs, using the fast-growing Mycobacterium smegmatis mc² 155 in a microtiter plate format was evaluated, based on phage viability assays. Methods: A variety of parameters were optimized before the study including the minimum incubation time for the drugs, phage and M. smegmatis mc² 155 to be in contact. An increase in phage numbers over 2 h was indicative that M. smegmatis mc² 155 is resistant to the drugs under investigation, however when phage numbers remained static, M. smegmatis mc² 155 found to …

The Effect Of Intracellular Zinc Levels In Escherichia Coli On Metallo-Β-Lactamase Activity, Jill Thompson

Graduate School of Biomedical Sciences Theses and Dissertations

Antibiotic resistance is a consequence of evolution via natural selection and poses a serious threat to the world's population. Escherichia coli, and other bacterial species, have acquired genes encoding Metallo-β-Lactamases (MBLs). MBLs are zinc-dependent enzymes that degrade most β-lactam antibiotics, and have emerged as important antibacterial resistance determinants in multidrug resistant pathogens. There are several different families of MBLs, and the major clinically relevant ones are Verona Integrated-encoded Metallo-β-Lactamases (VIMs), Imipenemases (IMPs), and New Delhi Metallo-β-Lactamases (NDMs). These enzymes confer high level resistance to penicillins, cephalosporins, and carbapenems, and are not inhibited by FDA-approved β-lactamase inhibitors. Variants of NDM have …

Lipoarabinomannan From Mycobacterium Smegmatis Stimulates An Inflammatory Response In Raw 264.7 Murine Macrophages, Aysha Zaman

Student Scholar Showcase

Macrophages are a key leukocyte in defense against Mycobacterium tuberculosis infection. The precise mechanism by which M. tuberculosis evades host macrophage defenses remains unknown, so understanding how macrophages interact with cell wall components of mycobacteria is critical. Lipoarabinomannan (LAM) is a glycolipid Toll-like receptor-2 (TLR-2) ligand found on the cell wall of mycobacteria, and is thought to contribute to the cell wall structural integrity. When LAM binds to TLR on host leukocytes, this activates cellular responses and phagocytosis by host macrophages. Nitric oxide production can be used as a measure of inflammatory response and can be evaluated via nitrite response …

Preconditioning Of The Tumor Microenvironment By Means Of Low Dose Chemotherapies For An Effective Immunotherapy Of Breast Cancer, Hussein F. Aqbi

Theses and Dissertations

Breast cancer mortality is mainly due to distant recurrence of the disease arising from dormant tumor cells established by cancer therapies. Patients who initially respond to cancer therapies often succumb to distant recurrence of the disease. It is not clear why people with the same type of breast cancer respond to treatments differently; some escape from dormancy and relapse earlier than others. In addition, some tumor clones respond to immunotherapy while others do not. We investigated how autophagy plays a role in accelerating or delaying recurrence of neu overexpressing mouse mammary carcinoma (MMC) following adriamycin (ADR) treatment, and in affecting …

Mastering Mycological Mysteries With Explorations Of Harpellales Associated With Culicidae And Other Dipterans In Idaho, Michael Mccormick

Boise State University Theses and Dissertations

Presented is the first field survey and laboratory-based study focused on Harpellales gut fungi found in Culicidae (mosquito) larvae collected from various parts of Idaho. Overall, 34 sites were sampled ranging from urban storm drains and irrigation puddles to pristine stream-side puddles. These sites yielded 17 different species of mosquitoes and three previously described species of gut fungi. Three species of mosquitoes were the first recorded observations as hosts of the following gut fungi: Culiseta alaskaensis was infested with Zancudomyces culisetae (from Renwyck Creek), Culex tarsalis with Smittium culicis (from Cottonwood Creek), and Ochleratus sp. with Smittium minutisporum (from Bear …

Characterization Of Tick Organic Anion Transporting Polypeptides (Oatps) Upon Bacterial And Viral Infections, Vikas Taank, Wenshou Zhou, Xuran Zhuang, John F. Anderson, Utpal Pal, Hameeda Sultana, Girish Neelakanta

Biological Sciences Faculty Publications

Background: Ixodes scapularis organic anion transporting polypeptides (OATPs) play important roles in tickrickettsial pathogen interactions. In this report, we characterized the role of these conserved molecules in ticks infected with either Lyme disease agent Borrelia burgdorferi or tick-borne Langat virus (LGTV), a pathogen closely related to tick-borne encephalitis virus (TBEV).

Results: Quantitative real-time polymerase chain reaction analysis revealed no significant changes in oatps gene expression upon infection with B. burgdorferi in unfed ticks. Synchronous infection of unfed nymphal ticks with LGTV in vitro revealed no significant changes in oatps gene expression. However, expression of specific oatps was significantly downregulated upon …

Triatomines: Trypanosomatids, Bacteria, And Viruses Potential Vectors? [Review], Caroline Barreto Vieira, Yanna Reis Praça, Kaio Luís Da Silva Bentes, Paula Beatriz Santiago, Sofia Marcelino Martins Silva, Gabriel Dos Santos Silva, Flávia Nader Motta, Izabela Marques Dorado Bastos, Jaime Martins De Santana, Carla Nunes De Araújo

Harold W. Manter Laboratory of Parasitology: Library Materials

Triatominae bugs are the vectors of Chagas disease, a major concern to public health especially in Latin America, where vector-borne Chagas disease has undergone resurgence due mainly to diminished triatomine control in many endemic municipalities. Although the majority of Triatominae species occurs in the Americas, species belonging to the genus Linshcosteus occur in India, and species belonging to the Triatoma rubrofasciata complex have been also identified in Africa, the Middle East, South-East Asia, and in the Western Pacific. Not all of Triatominae species have been found to be infected with Trypanosoma cruzi, but the possibility of establishing vector transmission …

Simulating Antibiotic Resistance In The Computer Lab And Biology Lab: Ideas For Undergraduate Projects, Anne E. Yust

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Type 2 Bovine Viral Diarrhea Virus NPro Suppresses Type I Interferon Pathway Signaling In Bovine Cells And Augments Bovine Respiratory Syncytial Virus Replication, Abdulrahman Abdulaziz A. Alkheraif

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

Bovine viral diarrhea virus (BVDV) and bovine respiratory syncytial virus (BRSV) infections contribute to the bovine respiratory disease complex (BRDC), which is a multi-factorial disorder involving co-infections of viruses and bacteria including mycoplasma. BRDC causes great economic losses to the United States feedlot industry. BVDV infection induces immunosuppression in infected animals. BVDV N^pro binds and degrades the transcription factor interferon regulatory factor-3 (IRF-3) and effectively blocks type I interferon (type I IFN) expression in host cells. BRSV nonstructural proteins, NS1 and NS2, block activation of IRF-3. In calves, concurrent infection with BVDV and BRSV resulted in more severe clinical …

Evolution Of Bordetella Pertussis Genome May Play A Role In The Increased Rate Of Whooping Cough Cases In The United States, Kevin Loftus

Senior Honors Projects, 2010-2019

Bordetella pertussis is the bacterium responsible for pertussis, a disease commonly referred to as whooping cough. Recently, pertussis has made a resurgence in the U.S. despite high-vaccination coverage. Possible causes of the increased number of pertussis cases include genetic evolution of B. pertussis, increased awareness of the disease, better laboratory diagnostics, and the switch from a whole-cellular (wP) vaccine to an acellular vaccine (aP) in the 1990s. Fortunately, just as B. pertussis is evolving, so is the arsenal of technologies used to understand and combat this pathogenic bacterium. Whole genome sequencing is one technology that helps researchers better understand …

Characterization Of The Interaction Between R. Conorii And Human Host Vitronectin In Rickettsial Pathogenesis, Abigail Inez Fish

LSU Doctoral Dissertations

Spotted Fever Group Rickettsia are inoculated into the mammalian host during hematophagous arthropod feeding. Once in the bloodstream and during dissemination, the survival of these pathogens is dependent upon their ability to evade innate host defenses until a proper cellular target is reached. The establishment of a successful infection also relies on the ability of the bacteria to attach and invade target cells, as failure to do so results in destruction of the bacterium. Rickettsia conorii expresses an outer membrane protein, Adr1, which binds the multifunctional human glycoprotein, vitronectin, to promote resistance to complement mediated killing. Homologs of Adr1 are …

In Vitro Assay Development As An Alternative To The Use Of Laboratory Animals For Measuring Clostridium Perfingens Type C Toxoid, Lauren M. Wilmes

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

Clostridium perfringens type C produces beta toxin, which is a primary virulence determinate that can cause necrotic enteritis in neonatal animals. Vaccines directed against C. perfringens toxins have shown to be efficacious in preventing disease. However, the production of a commercial vaccine requires not only an efficacious antigen, but also testing methods for quantifying antigens and potency on final product. This research was undertaken to fulfill a need for the reduction in small animal usage to produce and deliver vaccines. The current testing methods are performed in vivo according to the Code of Federal Regulations number 9 (9CFR) United …

Antibody Dependent Enhancement Of Visceral Leishmaniasis, Alan K. Mcnolty

All Master's Theses

Leishmaniasis is a parasitic disease caused by protozoans of the genus Leishmania. This vector-born disease, transmitted by biting phlebotomine sandflies, typically manifests in one of three ways. The cutaneous form of the disease is characterized by localized lesions of the skin and is by far the most common manifestation. The visceral form of the disease is caused by parasitic infiltration of internal organs, particularly the spleen, liver, and bone marrow. The mucocutaneous form is caused by parasitic infection of the mucosa in the nose or mouth. While cutaneous leishmaniasis (CL) is often self-healing, visceral leishmaniasis (VL) is fatal if …

Relationships Between Factors Influencing Biofilm Formation And Pathogen Retention In Complex Rhizosphere Microbial Communities, Aaron Coristine

Theses and Dissertations (Comprehensive)

Riparian wetlands are unique habitats facilitating all forms of life. The riverbanks of these environments provide ideal conditions for bacteria, plants, and higher organisms. Of particular interest to this research was the variation in microbial community structure at high, intermediate and poor water quality impacted areas. Assessing the capabilities of plants to retain microbial pathogens was identified. Root systems and corresponding soil are ideal locations for bacterial deposition, resulting in attachment at these areas. Biofilm production in these regions is important for long-term establishment, leading to persistence and potential naturalization. Opportunistic pathogens originating from mammalian fecal matter are introduced into …

Changing Antimalarial Drug Sensitivities In Uganda, Stephanie Alexis Rasmussen

Dissertations, Masters Theses, Capstones, and Culminating Projects

Dihydroartemisinin-piperaquine (DP) has demonstrated excellent efficacy for the treatment and prevention of malaria in Uganda. However, resistance to both components of this regimen has emerged in Southeast Asia. The efficacy of artemether-lumefantrine, the first-line regimen to treat malaria in Uganda, has also been excellent, but continued pressure may select for parasites with decreased sensitivity to lumefantrine. To gain insight into current drug sensitivity patterns, ex vivo sensitivities were assessed and genotypes previously associated with altered drug sensitivity were characterized for 58 isolates collected in Tororo, Uganda from subjects presenting in 2016 with malaria from the community or as part of …

Fluorescence-Reported Allelic Exchange Mutagenesis Reveals A Role For Chlamydia Trachomatis Tmea In Invasion That Is Independent Of Host Ahnak, M. J. Mckuen, Konrad E. Mueller, Y. S. Bae, Kenneth A. Fields

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Development of approaches to genetically manipulate Chlamydia is fostering important advances in understanding pathogenesis. Fluorescence-reported allelic exchange mutagenesis (FRAEM) now enables the complete deletion of specific genes in C. trachomatis L2. We have leveraged this technology to delete the coding sequences for a known type III effector. The evidence provided here indicates that CT694/CTL0063 is a virulence protein involved in chlamydial invasion. Based on our findings, we designate the gene product corresponding to ct694-ctl0063 translocated membrane-associated effector A (TmeA). Deletion of tmeA did not impact development of intracellular chlamydiae. However, the absence of TmeA manifested as a decrease in infectivity …

Mechanism Of Candida Albicans Biofilm And Virulence Inhibition By A Bacterial Secreted Factor, Carrie Graham

Dissertations and Theses (Open Access)

The human microbiome is a diverse polymicrobial population comprised of both fungi and bacteria. Perturbations of the normal microbiome can have a profound impact on health, including the development of infections. Exploitation of these polymicrobial interactions has the potential to provide novel treatment and prevention strategies for infectious diseases. Enterococcus faecalis, a Gram-positive bacterium, and Candida albicans, a polymorphic fungus, occupy overlapping niches as ubiquitous constituents of the gastrointestinal and oral microbiome. Both species are also amongst the most important and problematic, opportunistic nosocomial pathogens and are often co-isolated during infection. Surprisingly, these two species antagonize each other’s …

Phytochemical Screening And Determination Of Antibacterial, Anti-Tumorigenic And Dna Protection Ability Of Root Extracts Of Saussurea Lappa, Sughra Arif Minhas, Fida Muhammad Khan, Fakhar-I- Abbas, Abu Ul Hassan Faiz

Journal of Bioresource Management

Saussurea lappa is a traditionally well-known plant for its medicinal uses in different indigenous systems of medicine. It is widely used in the treatment of asthma, ulcer, stomach problems and inflammatory diseases. In current study the phytochemical screening of S. lappa showed the presence of sesquiterpenes, anthraquinones, lignans, alkaloids, flavonoids, glycosides and steroids. Antimicrobial potential of subject plant was also investigated against three bacterial strains and maximum antibacterial activity was observed by CEE against S. aureus, CAE against P. aeruginosa, while CME, CEE, EAE and PEE showed almost same significant activity against E. coli. The CME (1000 …

Trypanosome Lytic Factor Mediated Immunity Against Leishmania Sp., Jyoti Pant

Dissertations, Theses, and Capstone Projects

Trypanosome Lytic Factor (TLF) is an innate immunity complex that was originally discovered to protect against African Trypanosomes. The major components of TLF are Apolipoprotein A1 (APOA1), Apolipoprotein L1 (APOL1) and HPR (Haptoglobin Related Protein), where APOL1 is necessary and sufficient for trypanolysis. Recently we have shown that TLF ameliorates infections by cutaneous Leishmania species. Here we investigated the effect of different primate and human TLF against different Leishmania sp. Our result shows that TLF kills metacyclic promastigotes of cutaneous Leishmania sp. within immune cells such as neutrophils and macrophages by two different mechanism. Using transiently transfected and germline transgenic …

Range-Wide Prevalence And Impacts Of Pseudocercosporella Inconspicua On Lilium Grayi And An Assessment Of L. Superbum And L. Michauxii As Reservoirs, Cindy L. Barrett

Electronic Theses and Dissertations

Lilium grayi (Gray’s Lily), a southern Appalachian endemic species, is threatened by a Lilium-specific fungal pathogen, Pseudocercosporella inconspicua. The disease is characterized by tan lesions that can cause early senescence, while also lowering seed production and viability. This project tested for P. inconspicua conidia and accessed health at nine locations. The disease was present and ubiquitous across the range of L. grayi. Through identification of P. inconspicua conidia in the field, L. superbum (Turk’s Cap Lily) was identified as an additional host, while L. michauxii (Michaux’s Lily) was disease-free. However, infection was inducible in both species. With …